Continuous or discontinuous tranexamic acid effectively inhibits fibrinolysis in children undergoing cardiac surgery with cardiopulmonary bypass.

Tranexamic acid is given continuously or discontinuously as an anti-fibrinolytic therapy during cardiac surgery, but the effects on fibrinolysis parameters remain poorly investigated. We sought to assess the effects of continuous and discontinuous tranexamic acid on fibrinolysis parameters in children undergoing cardiac surgery with cardiopulmonary bypass (CPB). Children requiring cardiac surgery or repeat surgery by sternotomy with CPB for congenital heart disease were randomized to receive either continuous or discontinuous tranexamic acid. Blood tranexamic acid, D-dimers, tissue plasminogen activator (tPA), tPA-plasminogen activator inhibitor 1 (tPA-PAI1) complexes, fibrinogen and fibrin monomers were measured and compared to values obtained from children who did not receive tranexamic acid. Tranexamic acid inhibited the CPB-induced increase in D-dimers, with a similar potency between continuous and discontinuous regimens. Time courses for tPA, fibrin monomers, and fibrinogen were also similar for both regimen, and there was a significant difference in tPA-PAI1 complex concentrations at the end of surgery, which may be related to a significantly higher tranexamic acid concentration. Continuous and discontinuous regimen are suitable for an effective inhibition of fibrinolysis in children undergoing cardiac surgery with CPB, but the continuous regimen was previously shown to be more effective to maintain stable tranexamic acid concentrations.

Comparison of two doses of tranexamic acid in adults undergoing cardiac surgery with cardiopulmonary bypass.

BACKGROUND: The optimal dose of tranexamic acid (TA) is still an issue. The authors compared two doses of TA during cardiac surgery in a multicenter, double-blinded, randomized study. METHODS: Patients were stratified according to transfusion risk, then randomized to two TA doses: 10 mg/kg bolus followed by 1 mg·kg·h infusion (low dose) until the end of surgery or 30 mg/kg bolus followed by 16 mg·kg·h infusion (high dose). The primary endpoint was the incidence of blood product transfusion up to day 7. Secondary ones were incidences of transfusion for each type of blood product and amounts transfused, blood loss, repeat surgery, TA-related adverse events, and mortality. RESULTS: The low-dose group comprised 284 patients and the high-dose one 285. The primary endpoint was not significantly different between TA doses (63% for low dose vs. 60% for high dose; P = 0.3). With the high dose, a lower incidence of frozen plasma (18 vs. 26%; P = 0.03) and platelet concentrate (15 vs. 23%; P = 0.02) transfusions, lower amounts of blood products (2.5 ± 0.38 vs. 4.1 ± 0.39; P = 0.02), fresh frozen plasma (0.49 ± 0.14 vs.1.07 ± 0.14; P = 0.02), and platelet concentrates transfused (0.50 ± 0.15 vs. 1.13 ± 0.15; P = 0.02), lower blood loss (590 ± 50.4 vs. 820 ± 50.7; P = 0.01), and less repeat surgery (2.5 vs. 6%; P = 0.01) were observed. These results are more marked in patients with a high risk for transfusion. CONCLUSIONS: A high dose of TA does not reduce incidence of blood product transfusion up to day 7, but is more effective than a low dose to decrease transfusion needs, blood loss, and repeat surgery.

A practical tranexamic acid dosing scheme based on population pharmacokinetics in children undergoing cardiac surgery.

BACKGROUND: Pediatric cardiac surgery patients are at high risk for bleeding, and the antifibrinolytic drug tranexamic acid (TA) is often used to reduce blood loss. However, dosing schemes remain empirical as a consequence of the absence of pharmacokinetic study in this population. The authors' objectives were thus to investigate the population pharmacokinetics of TA in pediatric cardiac surgery patients during cardiopulmonary bypass (CPB). METHODS: Twenty-one patients were randomized to receive TA either continuously (10 mg/kg followed by an infusion of 1 mg · kg · h(-1) throughout the operation, and 10 mg/kg into the CPB) or discontinuously (10 mg/kg, then 10 mg/kg into the CPB and 10 mg · kg · h(-1) at the end of CPB). Serum concentrations were measured at eight time points with chromatography-mass spectrometry and the data were modeled using Monolix (Lixoft, Orsay, France). RESULTS: Tranexamic acid pharmacokinetics was ascribed to a two-compartment open model. The main covariate effects were body weight and CPB. Representative pharmacokinetic parameters adjusted to a 70-kg body weight were as follows: systemic clearance, 2.45 l/h; volume of distribution in the central compartment, 14.1 l; intercompartmental clearance, 5.74 l/h; and peripheral volume, 32.8 l. In accordance with this model, the authors proposed a weight-adjusted dosing scheme to maintain effective TA concentrations in children during surgery, consisting of one loading dose followed by a continuous infusion. CONCLUSIONS: The authors report for the first time the pharmacokinetics of TA in children undergoing cardiac surgery with CPB, and propose a dosing scheme for optimized TA administration in those children.

Pre- and postoperative magnetic resonance imaging in neonatal arterial switch operation using warm perfusion.

Neurological morbidity is a major concern in pediatric cardiac surgery. Cardiopulmonary bypass is one of the few modifiable factors affecting neurodevelopmental outcome. This study aimed to measure the incidence of abnormalities apparent by magnetic resonance imaging (MRI) after neonatal arterial switch operation using warm surgery. Neonates admitted for transposition of the great arteries underwent pre- and postoperative brain MRI. They were operated on using a warm perfusion method. The data collected included antenatal diagnosis, place of birth, gestational age, total maturation score as described by Childs, weight, cyanosis as assessed by minimal SpO(2) sustained for at least 10 min, balloon atrial septostomy, prostaglandin E1 infusion, need for neonatal intensive care, bypass time, time to extubation, and length of stay in intensive care. All of the MRI results were interpreted by the same senior specialist in pediatric neuroimaging, and lesions were classified as white matter injury, infarct, or hemorrhage. On preoperative exam, nine patients (42%) had one or more lesions, with infarct in four patients, white matter injury in four patients, and hemorrhage in five. We were unable to find any correlation between the data collected and brain injury. On postoperative exam, there was one new infarct, two new cases of white matter injury, and three cases of hemorrhage but no worsening of the preoperative lesions. Based on this initial experience with brain imaging, there is no deleterious effect of warm perfusion and no rationale to postpone surgery in neonates with "subclinical" brain injury.